title: Translational control of NKT cell cytokine production by p38 MAPK.
abstract: NKT cells are known to rapidly produce a large amount of cytokines upon activation. Although a number of signaling pathways that regulate the development of NKT cells have been identified, the signaling pathways involved in the regulation of NKT cell cytokine production remain unclear. In this study, we show that the p38 MAPK pathway is dispensable for the development of NKT cells. However, NKT cell cytokine production and NKT-mediated liver damage are highly dependent on activation of this pathway. p38 MAPK does not substantially affect cytokine gene expression in NKT cells, but it regulates the synthesis of cytokines through the Mnk-eIF4E pathway. Thus, in addition to gene expression, translational regulation by p38 MAPK could be a novel mechanism that contributes to the overall production of cytokine by NKT cells.
authors.affiliation: Division of Immunobiology, Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Viswas K
authors.initials: VK
authors.lastname: Nagaleekar
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: Idil
authors.initials: I
authors.lastname: Aktan
authors.forename: Alan
authors.initials: A
authors.lastname: Chant
authors.forename: Isaac W
authors.initials: IW
authors.lastname: Howe
authors.forename: Tina M
authors.initials: TM
authors.lastname: Thornton
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Benoit
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Boyson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D008107:Liver Diseases / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D048371:MAP Kinase Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D048669:MAP Kinase Kinase 6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D046188:Protein Modification, Translational / Q000276:immunology*
chemical_list: D016207:Cytokines; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse